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Metabolic rewiring and cellular reprogramming are trademarks of neoplastic initiation and progression in acute myeloid leukemia (AML). Metabolic alteration in leukemic cells is often genotype specific, with associated changes in epigenetic and functional factors resulting in the downstream upregulation or facilitation of oncogenic pathways. Targeting abnormal or disease-sustaining metabolic activities in AML provides a wide range of therapeutic opportunities, ideally with enhanced therapeutic windows and robust clinical efficacy. This review highlights the dysregulation of amino acid, nucleotide, lipid, and carbohydrate metabolism in AML; explores the role of key vitamins and enzymes that regulate these processes; and provides an overview of metabolism-directed therapies currently in use or development.

In view of the problems that the mechanical seal for the water pump is prone to deformation, friction and wear, and loss of sealing performance in the process of use, taking the temperature change of end surface as the research entry point, the temperature distribution, stress and strain diagram of rotating ring, and stationary ring are obtained by thermal-stress coupling simulation. The temperature change of stationary ring is studied by the experiments, and the friction state of end surface of rotating ring and stationary ring are observed. The results indicate that the test temperature of stationary ring is slightly lower than simulation temperature, which is related to the thermocouple fixed on the side of the stationary ring for temperature measurement. In addition, comparing the micro morphology of end surface of rotating ring before and after the experiment, it is found that there is significant plastic deformation on the inner diameter of rotating ring, which is related to the stress generated by the thermal-mechanical coupling of inner diameter of rotating ring exceeding the material limit, consistent with the simulation results.

Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.

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This article reviews the regulation of production of RBCs at several levels. We focus on the regulated expansion of burst-forming unit-erythroid erythroid progenitors by glucocorticoids and other factors that occur during chronic anemia, inflammation, and other conditions of stress. We also highlight the rapid production of RBCs by the coordinated regulation of terminal proliferation and differentiation of committed erythroid colony-forming unit-erythroid progenitors by external signals, such as erythropoietin and adhesion to a fibronectin matrix. We discuss the complex intracellular networks of coordinated gene regulation by transcription factors, chromatin modifiers, and miRNAs that regulate the different stages of erythropoiesis.

This article reviews the regulation of production of RBCs at several levels. We focus on the regulated expansion of burst-forming unit-erythroid erythroid progenitors by glucocorticoids and other factors that occur during chronic anemia, inflammation, and other conditions of stress. We also highlight the rapid production of RBCs by the coordinated regulation of terminal proliferation and differentiation of committed erythroid colony-forming unit-erythroid progenitors by external signals, such as erythropoietin and adhesion to a fibronectin matrix. We discuss the complex intracellular networks of coordinated gene regulation by transcription factors, chromatin modifiers, and miRNAs that regulate the different stages of erythropoiesis.

A neuro-fuzzy (NF)-based adaptive controller is presented in this paper for the trajectory tracking control of a flexible-link space manipulator. Based on the singular perturbation method and two time-scale decompositions, the dynamic model of a flexible space robot is reduced into a slow subsystem of an equivalent rigid-link arm and a fast subsystem of flexible mode. A dynamic NF adaptive controller based on dynamic inversion is presented for the tracking control of the equivalent rigid arm, while a fuzzy proportional-derivative (PD) controller is used to stabilize the elastic dynamics. Finally, experiment studies are carried out to show the viability and effectiveness of the proposed control approach.

The muscarinic acetylcholine receptor CHRM4 is a druggable target regulating the self-renewal of early erythroid progenitors.